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Initiation to end point: the multiple roles of fibroblast growth factors in neural development

Nature Reviews Neuroscience volume 8, pages 583–596 (2007)Cite this article

Key Points

  • FGFs are established as key players during neural induction and also during the induction of ectodermal placodes and possibly the neural crest.

  • FGFs are utilised in the posteriorization of the neural plate and then redeployed in several organizing centres to regulate further subdivision of the CNS.

  • The regulation of survival and differentiation by FGFs is a general theme during development. A mitogenic function may be more restricted within the developing nervous system.

  • The regulation and maintenance of several stem cell niches has been demonstrated in vivo, and FGFs are extensively used to direct neural stem cell development in vitro.

  • New roles for FGFs in both axon guidance and synaptogenesis have recently been identified.

  • There are clear associations for FGFs with human developmental diseases, notably Kallmann syndrome and 22q11 syndromes, and potential links with schizophrenia and Parkinson's disease.

Abstract

From a wealth of experimental findings, derived from both in vitro and in vivo experiments, it is becoming clear that fibroblast growth factors regulate processes that are central to all aspects of nervous system development. Some of these functions are well known, whereas others, such as the roles of these proteins in axon guidance and synaptogenesis, have been established only recently. The emergent picture is one of remarkable economy, in which this family of ligands is deployed and redeployed at successive developmental stages to sculpt the nervous system.

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Figure 1: Fibroblast growth factor (FGF) structure and phylogeny.
Figure 2: Fibroblast growth factor receptor (FGFR) structure.
Figure 3: Signalling through fibroblast growth factor receptors (FGFRs).
Figure 4: Sites of fibroblast growth factor (FGF) signalling during neural induction and patterning.
Figure 5: Fibroblast growth factor (FGF) functions in ectodermal placode development.
Figure 6: Fibroblast growth factor (FGF) functions during neural crest development.

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Acknowledgements

I apologize to my many colleagues whose work could not be included or cited directly due to a combination of the large scope of this Review and constraints of space. I would like to thank S. Cadman, A. Graham, C. Holt, J. Sanes and C. Stern for their insightful comments on individual sections of the manuscript, and give particular thanks to G. Fishell and K. Storey for commenting on the entire manuscript and to J. Sanes and K. Storey for providing data prior to publication. Work in my laboratory is funded by the Medical Research Council, the Wellcome Trust and Wyeth, and I was in receipt of a Fellowship from the Leverhulme Trust, which greatly facilitated the preparation of the manuscript.

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Glossary

Neural induction

The process by which signalling from an adjacent tissue specifies part of the embryonic ectoderm to form the neural plate.

Alternative splicing

Allows the production of different messenger RNAs from a single gene through the differential incorporation of exons into the mature transcript during splicing. Various mature proteins are frequently generated from a single gene.

Signal peptide

A short, generally amino-terminal, sequence that directs newly synthesized secretory or transmembrane proteins to and through the membranes of the endoplasmic reticulum.

Adaptor protein

An accessory to the main signalling proteins in a signal transduction pathway. Adaptor proteins tend to lack any intrinsic enzymatic activity themselves, but instead mediate the specific protein?protein interactions that drive the formation of protein complexes. Examples in FGF signalling include Shc and Grb2.

Hensen's node

The avian equivalent of the Spemann organizer, located at the anterior of the primitive streak (through which gastrulation occurs).

Spemann organizer

A signalling centre located on the dorsal side of an amphibian embryo that is capable of inducing new antero?posterior and dorso?ventral axes. The neural plate is one of the tissues it can induce from nearby cells. The concept of neural induction resulted from its discovery.

Neural plate

A continuous sheet of neural epithelial cells that forms after neural induction and gives rise to the central nervous system and the neural crest.

Organizer

A signalling centre that directs the development of all or part of the embryo and is capable of instructing several fate choices in nearby cells.

Shield

The zebrafish equivalent of the Spemann organizer, located, as in amphibians, on the dorsal side of the gastrulating embryo.

Motor neuron pool

A generally spindle-shaped and continuous group of motor neurons that are located at a specific position within the spinal cord or hindbrain. They innervate a single, identified muscle.

Hypomorphic mouse

A mouse that expresses less than the normal level of protein from a particular gene.

Neurotrophic factor

A factor, usually a protein, which is secreted by target tissues (for example, muscle, glial cells and across synapses) and which promotes neuronal survival.

Mitogen

An agent that induces mitosis, usually resulting in subsequent cell division.

Commissure

A tract of nerve fibres that passes from one side of the CNS to the other.

Active zone

A portion of the presynaptic membrane that faces the postsynaptic density across the synaptic cleft. It constitutes the site of synaptic vesicle clustering, docking and neurotransmitter release.

Hypogonadotropic hypogonadism

The absent or decreased function of the gonads, resulting from the absence of gonadotrophin releasing hormone, follicle stimulating hormone and luteinizing hormone.

Haploinsufficiency

A situation in which the loss of one copy (one allele) of a gene is sufficient to give rise to disease. Haploinsufficiency implies that no dominant-negative effect of the mutated gene product has to be invoked.

Synkinesia

The involuntary movement of muscles or limbs which accompanies a voluntary movement and sometimes results in identical bilateral movements called mirror movements.

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Mason, I. Initiation to end point: the multiple roles of fibroblast growth factors in neural development. Nat Rev Neurosci 8, 583–596 (2007). https://doi.org/10.1038/nrn2189

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